Sero prevalence of covid 19 i high risk population in viet nam

Author contributions: Tasnim Hasan: manuscript preparation, writing – first draft, writing – editing, data analysis Pham Ngoc Thach: investigation, project administration, writing – revi

Title: Sero-prevalence of SARS-CoV-2 in high-risk populations in Vietnam

Authors:

Tasnim Hasan 1,2 MBBS

Pham Ngoc Thach 3 PhD

Nguyen Thu Anh 2 PhD

Le Thi Thu Hien 2 MIPH

Le Van Duyet 3 PhD

Dang Thi Thuy 3 MD

Van Dinh Trang 3 PhD

Pham Ngoc Yen 2 MS

Nguyen Viet Ha 2 BPharm

Tran Linh Giang 2 BPharm

Nguyen Thi Cam Van 2 MD

Nguyen Trung Thanh 2 BSPH

Truong Quang Viet 4 MD

Dao Huu Than 4 MD

Le Thanh Chung 5 MD

Truong Tan Nam 5 MD

Vo Trung Hoang 6 MD

Le Thanh Phuc 7 MD

Nguyen Thanh Thao 8 MD

Luu Van Vinh 8 MPH

Nguyen Dai Vinh 9 MD

Brett Toelle 1,2,10 PhD

Greg J Fox 1,2 PhD

1- Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia 2006

2- The Woolcock Institute of Medical Research, Glebe, NSW, Australia 2037

3- National Hospital of Tropical Diseases, Hanoi, Vietnam

4- Hanoi Center for Disease Control (CDC), Hanoi, Vietnam

5- Centre for Disease Control Da Nang, Da Nang City, Vietnam

6- Centre for Disease Control Quang Nam, Quang Nam Province, Vietnam

7- Da Nang Lung Hospital, Da Nang City, Vietnam

8- Quang Nam Pham Ngoc Thach Hospital

9- Hoa Vang District Health Center, Da Nang City, Vietnam

10- Sydney Local Health District, NSW, Australia

11- South Western Sydney Clinical School, The University of New South Wales, Liverpool, NSW,

Australia

Corresponding author:

Professor Greg Fox

Room 5216, Level 2, Medical Foundation Building, K26

Conflicts of interest:

None declared

Funding:

This project was supported by a grant funded by the Australian Department of Foreign

Affairs and Trade, awarded in conjunction with the Australian National Health and Medical

Research Council (APP1153346)

Acknowledgements:

We acknowledge the contributions to this study made by healthcare workers from National

Hospital for Tropical Diseases, Quang Nam Pham Ngoc Thach Hospital, Da Nang Lung

Hospital, Centre for Disease Control in Hanoi, Danang and Quang Nam Provinces and Me

Linh, Thang Binh, Dien Ban and Hoa Vang District Health Centers in Vietnam We

acknowledge the valuable contributions the research staff of the Woolcock Institute of

Medical Research, Vietnam, and local partners to undertake the serology survey

Data sharing:

The data used for this research, including deidentified participant data and data dictionary,

are available from the corresponding author on request

Author contributions:

Tasnim Hasan: manuscript preparation, writing – first draft, writing – editing, data analysis

Pham Ngoc Thach: investigation, project administration, writing – review and editing

Nguyen Thu Anh: supervision, conceptualisation, data curation, writing - review and editing

Le Thi Thu Hien: supervision, data curation, investigation, project administration, writing – review

Le Van Duyet: investigation, project administration, writing – review and editing

Dang Thi Thuy: investigation, project administration, writing – review and editing

Van Dinh Trang: investigation, project administration, writing – review and editing

Pham Ngoc Yen: investigation, project administration, writing – review and editing

Nguyen Viet Ha: data curation, investigation, project administration, writing – review and editing

Tran Linh Giang: data curation, investigation, project administration, writing – review and editing

Nguyen Thi Cam Van: data curation, investigation, project administration, writing – review and

editing

Nguyen Trung Thanh: data curation, investigation, project administration, writing – review and

editing

Truong Quang Viet: investigation, project administration, writing – review and editing

Dao Huu Than: investigation, project administration, writing – review and editing

Le Thanh Chung: investigation, project administration, writing – review and editing

Truong Tan Nam: investigation, project administration, writing – review and editing

Vo Trung Hoang: investigation, project administration, writing – review and editing

Le Thanh Phuc: investigation, project administration, writing – review and editing

Nguyen Thanh Thao: investigation, project administration, writing – review and editing

Luu Van Vinh: investigation, project administration, writing – review and editing

Nguyen Dai Vinh: investigation, project administration, writing – review and editing

Brett Toelle: conceptualisation, supervision, data curation, writing – review and editing

Guy B Marks: conceptualisation, supervision, writing – review and editing

Greg J Fox: conceptualisation, supervision, writing – review and editing

Preprint not peer reviewed

Background: As a response to the coronavirus disease 2019 (COVID-19) pandemic,

Vietnam enforced strict quarantine, contact tracing and physical distancing policies By

December 2020, this strategy resulted in one of the lowest numbers of individuals infected

with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) cases globally This

study aimed to determine the prevalence of SARS-CoV-2 antibody positivity among

high-risk populations in Vietnam

Methods: A prevalence survey was undertaken within four communities in northern and

central Vietnam, where at least two COVID-19 cases had been confirmed Participants were

classified according to the location of exposure: household contacts, close contacts,

community members, and healthcare workers (HCWs) responsible for treating COVID-19

cases Participants completed a baseline questionnaire that evaluated exposure history

SARS-CoV-2 IgG antibodies were quantified using a commercially available assay

Results: 3049 community members and 149 health care workers provided consent to

participate Among enrolled community members, 27 (0·9%) were household contacts and 53

(1·7%) were close contacts Serology was performed in 3034 individuals Among 13

individuals who were seropositive (0·4%), five household contacts (5/27, 18·5%), one close

contact (1/53, 1·9%), and seven community members (7/2954, 0·2%) had detectable

SARS-CoV-2 antibodies All HCWs were negative for SARS-SARS-CoV-2 antibodies Participants were

tested a median of 15·1 (interquartile range 14·9 to 15·2) weeks after exposure

Conclusion: The presence of SARS-CoV-2 antibodies in high-risk communities and

healthcare workers was low in communities in Vietnam with known COVID-19 cases The

public health response to the COVID-19 pandemic in Vietnam has been effective in limiting

community transmission of SARS-CoV-2

Preprint not peer reviewed

Research in context

Evidence before this study

Vietnam is one of the few countries which has effectively controlled the COVID-19

pandemic with very low reported case numbers, mortality However, there is speculation as to

whether official figures may underestimate the epidemiological extent of infection in

Vietnam Sero-prevalence studies is a method which can provide a surrogate measure of the

extent of SARS-CoV-2 infection in the general population Although there are several studies

looking at the prevalence of SARS-CoV-2 antibodies in populations around the world, no

sero-prevelance studies have been performed in the Vietnamese community A limited

number of studies which specifically look at prevalence of antibodies in high-risk contacts

including household contacts, close contacts and community members The determination of

sero-prevalence in high-risk populations in Vietnam can provide an insight into

understanding if the strict physical distancing and quarantine policies have been effective in

controlling community transmission of COVID-19 in Vietnam

Added value of this study

The overall prevalence of SARS-CoV-2 antibodies in high-risk communities was low – just

0·4% As expected, household contacts of confirmed COVID-19 cases, had a higher

prevalence of antibodies (18·5%), while the prevalence was lower in close contacts (1·9%)

and members of the general community (0·2%) The absence of sero-positivity among health

care workers is unique, with only one other study, also in Vietnam, being able to demonstrate

the lack of SARS-CoV-2 antibodies in health care workers who are directly involved in the

care of COVID-19 patients The low seroprevalence of SARS-CoV-2 antibodies in high-risk

Preprint not peer reviewed

Vietnamese populations confirms the effectiveness of rapidly enforced strict policies

implemented by the Vietnamese government in controlling the COVID-19 pandemic

Implications of all the available evidence

This study provides a strong message of the importance of government policies to limit the

spread of the COVID-19 pandemic Furthermore, it affirms that control of COVID-19 is

possible, even in a densely populated, moderately-resourced setting

Preprint not peer reviewed

Vietnam is a populous southeast Asian country, bordering China By December 2020, the

country had reported among the lowest number of cases of infection with severe acute

quarantine of returning travellers, and strict isolation of proven cases as well as their first-

December 2020, 1,351 microbiologically confirmed cases of coronavirus disease of 2019

possible that the number of reported cases may be an under-estimate the true incidence of

disease This is because some people with the infection may not have been tested as they did

not have symptoms, did not seek care, or were not able to access a virus-detection test

Serological tests measure the antibody response to the virus, with a response evident from

to evaluate the true cumulative incidence of infection with SARS-CoV-2 and, by comparison

the substantial variation in countries’ experience of the pandemic Countries implementing

successful public health measures to reduce transmission – including physical distancing,

effective quarantining of high-risk individuals and strict border controls – have reported a

low prevalence of SARS-CoV-2 antibodies (seroprevalence) in the population For example,

sero-prevalence rates of less than 1% in the general population were reported in Greece,

including northern Europe and North America, the seroprevalence of infection in sampled

of confirmatory testing, for every confirmed SARS-CoV-2 case in the community, antibody

Health care workers (HCW) exposed to patients with COVID-19 are often reported to be at

Vietnam shares a 1,300km northern border with China The first case of COVID-19 was

Within eight weeks, Vietnam had closed its national borders, introduced quarantine

procedures, closed all schools and businesses, implemented physical distancing policies, and

confirmed cases were required to enter mandatory quarantine at public facilities following

risk assessment

The presence of undetected transmission in Vietnam is unknown This study aimed to

measure the prevalence of serological response to SARS-CoV-2 in communities where cases

of COVID-19 were reported and among household contacts and healthcare workers exposed

to patients known to have COVID-19

Methods

Study design and setting

A cross-sectional study was performed in three provinces of Vietnam in which community

Southeast Asia with a population of 96 million Within each of its 63 provinces, healthcare is

delivered by the provincial government’s Department of Health with support from the

national Ministry of Health Each province is further sub-divided into districts, communes,

and sub-communes Sub-communes usually have a population of between 500 and 2000

people

The first outbreak of COVID-19 occurred in northern Vietnam in January 2020

with no detected community transmission of COVID-19, on 25 July 2020, Vietnam reported

a new case of COVID-19 in a patient presenting with an acute respiratory illness to Da Nang

Provincial Hospital This outbreak in central Vietnam quickly spread into the local

community and 13 other provinces Despite an increase in community transmission, the

outbreak was effectively controlled within a 40-day period, with a co-ordinated public health

response Supplement 1 shows the number of cases detected in affected provinces over time

Site selection

Sub-communes were eligible for inclusion in this study if they had at least two cases of

COVID-19 confirmed based upon real time reverse transcriptase polymerase chain reaction

(rRT-PCR) testing of nasal/ throat swabs Sites were selected to reflect both urban and rural

settings and to include sub-communes with the highest cases numbers (Supplement 2)

Finally, four communes were selected These were in northern Vietnam: (i) Hoi

sub-commune in Ha Loi sub-commune, Me Linh district, Hanoi Capital (where five cases of known

COVID-19 were diagnosed in April 2020); and central Vietnam: (i) Giao Ai sub-commune in

Dien Hong commune, Dien Ban, Quang Nam Province (three cases of known COVID-19 in

known COVID-19 between July and August July 2020), (iii) Le Son Nam sub-commune in

Hoa Tien commune, Da Nang (eight cases in August 2020)

Study population

All people residing in each sub-commune during the outbreaks who were aged 5 years and

older and who were capable of giving consent, or having consent given by a guardian (for

children <16 years), were eligible to participate The names and addresses of household

contacts and close contacts of COVID-19 cases were obtained from the local Centres for

Disease Control (CDC) Enrolled participants were classified as close contacts, household

contacts, or general community members Close contacts of a COVID-19 cases were those

who been within a two-meter distance of the COVID-19 case for at least 15 minutes or had

been present in the same room for at least two hours during the infectious period (that is,

from 48-hours prior to symptom onset or diagnosis until the person with confirmed

COVID-19 case was placed in isolation) Household contacts of a COVID-COVID-19 case were those who

were not close contacts but who were living in the same dwelling and sharing meals or

kitchen with a COVID-19 case during the infectious period General community members

were those who were not close or household contacts of COVID-19 case but were living in

the same sub-commune as the COVID-19 case

Individuals were excluded if they were unable or refused to provide consent, were less than

five years of age or if they were a household/community member who had not stayed in the

same house/sub-commune during the infectious period Individuals who were documented as

PCR-positive for COVID-19 during the outbreaks were excluded from testing

HCW were enrolled at two health care facilities: Da Nang Lung Hospital, a provincial

hospital in Da Nang, and Hoa Vang District Hospital, a district hospital in Da Nang All

HCW enrolled were directly involved in the care of COVID-19 cases Doctors, nurses, allied

health workers, laboratory staff, and any other ancillary staff who involved in patient care

were included

Study questionnaire

Interviews were conducted with each study participant between September and November

2020 Data were collected about participants’ age, gender, contact status and history of

comorbidities, and medications Travel to Da Nang and Quang Nam, two provinces in central

Vietnam in which the second outbreak occurred, was separately recorded for people in Hanoi

The proximity, duration, and number of exposures with a COVID-19 cases within the

infectious period were also recorded Surveys were conducted and recorded using a REDCap

database

Serology testing

Blood was drawn for serological testing a median of 15·1 weeks (IQR 14·9 – 15·2) after

confirmation of a COVID-19 case in the community or household Where the result of assay

was indeterminate, the test was repeated We used the Elecsys Anti-SARS-CoV-2 serology

assay on the cobas platform (Roche Diagnostics International Ltd, Rotkreutz, Switzerland)

This assay has been shown to have a sensitivity and specificity of 96·8% and 99·8%,

performed in accordance with the manufacturer’s instructions

Preprint not peer reviewed

PCR testing for SARS-CoV-2

Participants, including HCWs who were symptomatic at the time of the survey, were offered

Analysis

Descriptive statistics were calculated, stratified by districts, for each category of individual –

household contact, close contact, community member, and HCW

Ethical issues

Ethical approval was obtained from the Human Research Ethics Committees of the

University of Sydney (HREC 2020/415) and Biomedical Research Ethics Committee of the

National Hospital for Tropical Diseases (No 10/HDDD-NDTU and No 18/HDDD-NDTU)

Consent was documented electronically using a tablet computer In accordance with local

expectations, all COVID-19 patients and other participants were provided with monetary

compensation for their participation, equivalent to approximately US$4·30 and US$2·20,

respectively

Results

A total of 3,049 individuals of 3747eligible (81·4%) provided consent for the study and blood

samples for serology were collected from 3,034 of these (99·5% of those consenting and

81·0% of eligible) The demographic, epidemiological, and clinical features of study

participants, classified by sub-commune, are presented in Table 1 Most participants (2,969)

and 53 were close contacts (1·7%) The median age of the population was 37 (interquartile

range (IQR) 19 – 53) Comorbidities were reported by 717 (23·5%) of participants, with

smoking being the most common comorbidity

Only one had travelled outside of Vietnam since January 2020 Almost 20% had travelled

within Vietnam since the onset of the pandemic Most local travel had been conducted using

private vehicles

Symptoms and actions

Only 162 (5·3%) study participants had reported any relevant symptoms between January

2020 and interview date The median number of symptoms reported was 1 (IQR 1-2) The

most common symptoms were sore throat, rhinorrhea, headache, and fatigue When

symptoms became evident, the most common action was to seek advice from the local

pharmacist, although many had waited for their symptoms to resolve spontaneously Most

individuals reported increased hand washing, the use of face masks, and a reduction in

attending social gatherings, over the course of the year (Table 1)

Details of exposure

Most exposure to COVID-19 cases took place at home Other settings in which community

members had exposure to COVID-19 patients included cafes, the marketplace, and at work

(Table 2) A small number of participants were exposed to COVID-19 patients at health care

facilities, including one individual who had exposure at a dialysis centre over several days

The number of COVID-19 contacts varied by sub-commune, with those who were household

contacts in Luu Minh commune having an average of 4·3 household COVID-19 contacts For

19 cases The duration of exposure with confirmed COVID-19 cases varied from 15 minutes

to 24 hours, with longer exposure generally reported by those who were household contacts

Health care workers

One hundred and forty-eight health care workers had direct exposure to COVID-19 cases

between two hospitals were included (Table 3) The median number of hours of contact with

a confirmed case per day was 6 hours, and healthcare workers reported a median of 40 days

(IQR 30-48·5) working in a healthcare setting where patients with COVID-19 were present

Over half of the HCWs were nurses and a quarter were doctors Twenty-nine (19·5%)

individuals reported any relevant symptoms between January 2020 and interview date The

median number of symptoms was two (IQR 1-2) Only 13 (8·7%) healthcare workers

reported comorbidities

Serology

Only 13 of 3,034 participants (0·4%) had detectable IgG antibodies to SARS-CoV-2 The

sero-positive participants included five of 27 (18·5%) household contacts, one of 53 (1·9%)

close contacts, and seven of 2,954 (0·2%) community members (Table 4) Of 148 HCW who

had serology performed, none had detectable antibodies (Table 3)

The median age of sero-positive participants was 35 (IQR 22-49), and seven (53·8%) were

female (Table 5) Three sero-positive participants were under 15 years of age A separate

three positive individuals were from the same household The remaining ten

sero-positive participants were each from different households No serosero-positive individuals had

travelled outside of Vietnam, and none of those in the north had travelled to Da Nang or

Vietnam, in three trips – all of which were by bus, however none had travelled to areas where

there were known COVID-19 outbreaks

Six of the 13 people with a positive serological test, including the five close contacts and one

household contact, were aware of exposure to a known COVID-19 case One individual had

contact with four COVID-19 cases while these four cases were infectious, one individual had

two such contacts and four sero-positive individuals had contact with one COVID-19 case

while the contact was infectious The average duration of contact with known COVID-19

cases while infectious was 6·45 hours One sero-positive individual had symptoms at the time

of community exposure (headache and conjunctivitis) during the community outbreak and

exposure in Hoi District in northern Vietnam in April These known household contacts and

close contacts were all quarantined after exposure However, the remaining seven

sero-positive participants, who were classified as community contacts, were not aware of their

exposure to a known COVID-19 case and local policy did not require compulsory

facility-based quarantine for community contacts However, people living in the same sub-commune

as a COVID-19 case (that is, community contacts) were encouraged to remain in home

isolation

Sixty-seven individuals had PCR performed as part of the study due to the presence

symptoms at the time of screening All these PCR tests were negative

Discussion

This survey of populations at high risk of infection with COVID-19 in Vietnam revealed a

low prevalence of SARS-CoV-2 antibodies, establishing that the local public health measures

the prevalence of antibodies to SARS-CoV-2 was high in household contacts of confirmed

COVID-19 cases, the overall prevalence of antibodies in the general population in these four

high-risk communities was just 0·4% Remarkably, all tested HCW who worked in facilities

managing COVID-19 patients had undetectable antibodies to SARS-CoV-2

The sero-prevalence of SARS-CoV-2 antibodies among people who were residents of the

sub-communes in which confirmed COVID-19 cases had been diagnosed, but were not

household or close contacts, was found to be just 0·2% Most published serological surveys

studies have evaluated community transmission and each of these has also found a low rate of

community transmission In high-prevalence European contexts the community prevalence

lower than that in other settings, suggesting that policies of isolating individuals with

COVID-19 at the time of diagnosis, and policies to encourage community members to remain

in isolation at home, have been effective in preventing the spread of infection into the

community

Transmission within households is an important factor in the spread of COVID-19 In this

study 18·5% of household contacts were sero-positive for SARS-CoV-2 antibodies Other

studies have found household prevalence of SARS-CoV-2 infection to be between 5·9 to

were no household contacts with detectable antibody levels In Vietnam household contacts

also underwent compulsory facility-based quarantine and this may have been an important